Targeting patients undergoing angioplasty for thrombus inhibition: a cost-effectiveness and decision support model.

BACKGROUND: In recent clinical trials, glycoprotein IIb/IIIa blockers have demonstrated effectiveness in preventing adverse events after angioplasty in high-risk patients. However, uncertainty exists regarding the cost-effective selection of patients to receive antiplatelet therapy. METHODS AND RESULTS: All 4962 patients at Emory University Hospitals who underwent coronary intervention procedures (n=6062) from 1993 to 1995 were studied. Multivariate models to predict death and the composite of death, Q-wave and non-Q-wave myocardial infarction, and emergency additional revascularization were developed. Hospital costs and professional costs were determined. A cost-effectiveness analysis with therapy targeted to high-risk patients was performed. If patients with a >5% probability of events received antiplatelet therapy that reduced events by 24% and cost $1000, 40.1% of patients would receive therapy; complications would be reduced from 6.39% to 5.37%, and cost would increase $261 from $10343 to $10604, or $25504 per event prevented. The marginal cost per event prevented by moving from a 7% to a 5% probability of an event cutoff would be $57 799. CONCLUSIONS: For high-risk patients, there may be cost savings; for low-risk patients, therapy may not be cost effective; and for patients in the midrange (between 5% and 7% probability of an adverse event), events may be prevented at an acceptable level of cost.

Economic impact of GPIIB/IIIA blockade after high-risk angioplasty: results from the RESTORE trial. Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis.

OBJECTIVE: This study was conducted to assess the impact of GPIIb/IIIa blockade with tirofiban on costs during the initial hospitalization and at 30 days among patients undergoing high-risk coronary angioplasty. BACKGROUND: GPIIb/IIIa blockers are a new class of compounds that have been shown in clinical studies to prevent complications after high-risk angioplasty. METHODS: The RESTORE trial was a multinational, blinded placebo-controlled study of 2,197 patients randomized to tirofiban or placebo following coronary angioplasty. This economic assessment was a prospective substudy of the RESTORE trial, and included 1,920 patients enrolled in the U.S. Costs were estimated for the U.S. cohort based on their utilization of healthcare resources and on costs measured directly in 820 U.S. patients at 30 sites. RESULTS: There was a 36% difference in the rate of the composite event of death, myocardial infarction (MI) and revascularization at two days between tirofiban and placebo (8% vs. 12%, p = 0.002). This difference was attributed to a reduction in nonfatal MI, repeat angioplasty, coronary surgery and stent placement. These clinical benefits followed a similar trend at 30 days, with a 16% reduction in the composite event (p = 0.10). In-hospital cost, including professional and study drug costs, was $12,145 +/- 5,882 with placebo versus $12,230 +/- 5,527 with tirofiban (p = 0.75). The 30-day cost was $12,402 +/- 6,147 with placebo versus $12,446 +/- 5,814 with tirofiban (p = 0.87). CONCLUSIONS: Tirofiban has been shown to decrease in-hospital and possibly 30-day events after high-risk angioplasty. The beneficial clinical effects of tirofiban in high-risk patients can be achieved at no increased cost.

Reduced coronary events in simvastatin-treated patients with coronary heart disease and diabetes or impaired fasting glucose levels: subgroup analyses in the Scandinavian Simvastatin Survival Study.

BACKGROUND: Patients with diabetes mellitus (DM) have a marked increase in coronary heart disease (CHD) events relative to those without DM. In a previous report from the Scandinavian Simvastatin Survival Study using a clinical case definition of DM (n = 202), simvastatin-treated patients had significantly fewer CHD events compared with placebo-treated control subjects. OBJECTIVE: To examine the effect of simvastatin therapy on CHD in patients with DM and impaired fasting glucose levels. METHODS: Using the 1997 American Diabetes Association diagnostic criteria, we assessed the effect of simvastatin therapy post hoc for an average of 5.4 years in Scandinavian Simvastatin Survival Study patients with normal fasting glucose (n = 3237), impaired fasting glucose (n = 678), and DM (n = 483). RESULTS: Simvastatin-treated patients with DM had significantly reduced numbers of major coronary events (relative risk [RR] = 0.58; P = .001) and revascularizations (RR = 0.52; P = .005). Total (RR = 0.79; P = .34) and coronary (RR = 0.72; P = .26) mortality were also reduced in DM, but not significantly, due to small sample size. In impaired fasting glucose (IFG) subjects, simvastatin use significantly reduced the number of major coronary events (RR = 0.62; P = .003), revascularizations (RR = 0.57; P = .009), and total (RR = 0.57; P = .02) and coronary (RR = 0.45; P = .007) mortality. CONCLUSION: Our results extend previous findings in patients with DM to a larger cohort, confirming the benefit of cholesterol lowering with simvastatin treatment on CHD events. In addition, significant decreases in total mortality, major coronary events, and revascularizations were observed in simvastatin-treated patients with impaired fasting glucose levels. These results strongly support the concept that cholesterol lowering with simvastatin therapy improves the prognosis of patients with elevated fasting glucose levels (> or =6.0 mmol/L [> or =110 mg/ dL]) or DM and known CHD.

Utilization of oral hypoglycemic agents in a drug-insured U.S. population.

OBJECTIVE: Clinical trials provide information regarding the safety and efficacy of medications used to manage type 2 diabetes but do not elucidate drug effectiveness in a typical managed care environment. The aim of this study was to characterize "real-world" drug utilization patterns from both a prescriber and a patient perspective. RESEARCH DESIGN AND METHODS: We conducted a retrospective analysis of a large administrative pharmacy claims database, using data on continuously pharmacy benefit-eligible members prescribed oral hypoglycemic agents (OHAs). RESULTS: The 12-month persistence rate for the OHA cohort was low, ranging from 31% for alpha-glucosidase inhibitors to 60% for metformin; compliance rates varied between 70 and 80%. During the first 12 months of therapy, 36% of the patients remaining on therapy at 12 months had one or more therapy modifications. The mean number of therapy changes increased with the length of patient follow-up, with more than half of all patients experiencing at least one therapy change over the duration of follow-up. CONCLUSIONS: These findings document the wide variation in utilization patterns associated with pharmacological management of type 2 diabetes, suggesting that opportunity exists to optimize its pharmacological management.

Effect of simvastatin treatment on cardiovascular resource utilization in impaired fasting glucose and diabetes. Findings from the Scandinavian Simvastatin Survival Study.

OBJECTIVE: The Scandinavian Simvastatin Survival Study showed that simvastatin treatment reduced cardiovascular events in hypercholesterolemic subjects with coronary heart disease. The clinical benefits of therapy were similar in all three subgroups: normal fasting glucose (NFG, n = 3,237), impaired fasting glucose (IFG, n = 678), and diabetes (n = 483). This analysis compared the costs of simvastatin treatment with the costs of cardiovascular disease-related hospitalizations in the three subgroups. RESEARCH DESIGN AND METHODS: The cost of simvastatin treatment was defined as the average retail price and the cost of drug safety monitoring and adverse experiences. The costs of cardiovascular disease-related hospitalizations were determined by actual rates of hospitalization and 1995 MEDSTAT diagnosis-related group costs. RESULTS: Within trial, simvastatin treatment cost approximately $6,000 per patient. Simvastatin treatment reduced cardiovascular disease-related hospitalizations by 23% in NFG (P = 0.001), 30% in IFG (P = 0.015), and 40% in diabetic subjects (P = 0.007) within trial (median follow-up of 5.4 years). Average length of stay was reduced by 2.4 days in diabetic subjects (P = 0.021). Total cardiovascular disease-related hospital days were reduced by 28% (P < 0.001) in NFG, 38% (P = 0.005) in IFG, and 55% (P < 0.001) in diabetic subjects. For NFG subjects, simvastatin reduced the average cost of cardiovascular disease-related hospitalizations by $3,585, which offset 60% of the cost of simvastatin therapy. For IFG subjects, average cardiovascular disease-related hospitalization costs were reduced by $4,478, which offset 74% of the drug cost. For diabetic subjects, there was a net cost savings of $1,801 per subject within trial. CONCLUSIONS: Simvastatin significantly reduced cardiovascular disease-related hospitalizations and total hospital days for all three groups and significantly reduced length of stay for the diabetic group in addition to providing significant clinical benefits. The benefits were greatest in the diabetic group, with estimated cost savings within trial from simvastatin treatment.

Prognosis after hospitalization for acute myocardial infarction not accompanied by typical ischemic chest pain. The Multicenter Diltiazem Postinfarction Trial Research Group.

PURPOSE: Although ischemic-type chest pain generally identifies acute myocardial infarction (AMI), some patients are hospitalized for AMI without this symptom. Long-term mortality and morbidity after AMI presenting with alternative warning symptoms have not been examined previously. We therefore assessed the prognostic implications of the absence of typical chest pain as well as other recognized risk predictors in patients hospitalized with AMI. PATIENTS AND METHODS: Data were obtained during the Multicenter Diltiazem Postinfarction Trial. Pain status and other baseline characteristics were determined prospectively by study coordinators according to simple, prespecified criteria. Patients were then examined every 3 to 4 months until trial completion. We applied chi-square methods, life-table analysis, and multivariate analysis to assess the strength and independence of prognostic power associated with each baseline variable. RESULTS: Of 2,464 patients enrolled 3 to 15 days after enzyme-documented AMI, 115 patients lacked typical ischemic-type chest in on presentation (the "nonpainful" group). After 25 months' mean follow-up, cardiac mortality was 20% for nonpainful patients and 10% for 2,349 patients with typical pain (the "painful" group), P < 0.001. Similar increments were seen in total deaths (27% nonpainful versus 13% painful, P < 0.001) and cardiac events, namely, cardiac death or nonfatal reinfarction (24% nonpainful versus 17% painful, P = 0.001). Late congestive heart failure was more frequent (17% nonpainful versus 7% painful, P < 0.001), but unstable angina was less (6% nonpainful versus 16% painful, P = 0.005). At outset, nonpainful patients had more left ventricular dysfunction and diabetes mellitus. However, nonpainful AMI predicted worse outcome even when these problems were absent. Logistic regression confirmed greater cardiac death risk in the nonpainful group (hazard ratio = 2.05) and showed that predictive power of nonpainful status was independent of baseline ejection fraction, Holter data, concomitant diabetes mellitus, and other covariates. CONCLUSIONS: Patients hospitalized with nonpainful AMI are much more likely to experience late cardiac death or congestive heart failure than are patients with painful AMI. In part, this probably reflects more ventricular damage with alternative warning symptoms such as dyspnea. However, our data suggest that defective perception of warning pain also provides a long-term risk to life that is independent of previously known predictors of poor outcome.

Noninvasive and angiographic evaluation of coronary artery disease in patients with peripheral vascular disease.

The accuracy of exercise testing for detection of coronary artery disease in a population with a high incidence of claudication was evaluated in 58 consecutive patients with abdominal aortic aneurysms or lower extremity occlusive disease. Each patient was evaluated by history and physical examination, symptom-limited testing with exercise treadmill, arm ergometry and exercise radionuclide ventriculography. An algorithm was designed that retrospectively examined the results of each test in a stepwise fashion to simulate a clinical decision-making process. The results of the clinical examination, each of the exercise tests and the noninvasive diagnostic algorithm were compared with the results of coronary arteriography. The predictive accuracy of the clinical evaluation was 36%, treadmill stress testing 57%, treadmill stress plus arm ergometry 74%, exercise radionuclide ventriculography 57% and the noninvasive diagnostic algorithm 89%. When discriminant analysis was applied to all of the exercise variables, no individual test improved the accuracy of the noninvasive diagnostic algorithm. When the analysis considered only individual variables without the algorithm, the model correctly classified only 67% of the patients. Thus, accurate noninvasive evaluation of coronary artery disease is possible in patients with severe peripheral vascular disease when care is taken to design exercise protocols that allow adequate stress on the cardiovascular system.

Costs of coronary restenosis (Lovastatin Restenosis Trial).

Within the Lovastatin Restenosis Trial, restenosis has been clearly shown to increase resource utilization and costs. While it is not possible to generalize these results to other patient populations, it is clear that successful efforts to decrease restenosis will certainly improve efficacy while decreasing follow-up costs and increasing the cost-effectiveness of intervention in the coronaries.

Long-term safety and efficacy profile of simvastatin.

Simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, has been administered to approximately 2,400 patients with primary hypercholesterolemia with a mean follow-up of 1 year in controlled clinical studies and their open extensions. Approximately 10% of this population received simvastatin for a period of greater than or equal to 2 years. The population on whom this safety analysis is based had a mean age of 50 years; 62% were men and approximately 27% had preexisting coronary artery disease. Simvastatin was titrated to the maximal daily dose of 40 mg each evening in 56% of the study population (last recorded dose). The most frequently reported drug-related clinical adverse experiences were constipation (2.5%), abdominal pain (2.2%), flatulence (2.0%) and headaches (1%). Persistent elevations of serum transaminase levels greater than 3 times the upper limit of normal were observed in only 1% of this cohort with only 0.1% of the total population requiring discontinuation of therapy. There were no clinically apparent episodes of hepatitis. Discontinuation of therapy due to myopathy was extremely rare (0.08%). Only minimal increases in the frequency of lens opacities (1%) were observed from baseline to the last lens examination during follow-up, consistent with the expected increase in lens opacity development due to normal aging. Patients who were greater than or equal to 65 years old had a clinical and laboratory safety profile comparable to the nonelderly population.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggressive lipid lowering in postcoronary angioplasty patients with elevated cholesterol (the Lovastatin Restenosis Trial).

A substudy of the Lovastatin Restenosis Trial in patients with elevated cholesterol (>200 mg/dl) showed no evidence of an effect of aggressive lipid lowering on restenosis, confirming the results of the main trial.

Effect of lovastatin on cardiovascular resource utilization and costs in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). AFCAPS/TexCAPS Research Group.

This cost-consequences analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study compares the costs of lovastatin treatment with the costs of cardiovascular hospitalizations and procedures. The cost of lovastatin treatment was defined as the average retail price and the cost of drug safety monitoring and adverse experiences. Costs were determined by actual rates of hospitalizations and procedures. Within a trial, lovastatin treatment cost approximately $4,654/patient. Lovastatin treatment significantly reduced the cumulative rate of cardiovascular hospitalizations and procedures (p = 0.002). Over the duration of the study, the cumulative number of cardiovascular hospitalizations and related therapeutic procedures was significantly reduced by 29%. The time to first cardiovascular-related hospitalization or procedure was significantly extended by lovastatin (p = 0.002). Lovastatin reduced the frequency of cardiovascular hospitalization (28%), and cardiovascular therapeutic (32%) and diagnostic procedures (23%). Among therapeutic procedures, treatment reduced coronary artery bypass graft surgery by 19% and percutaneous transluminal coronary angioplasty by 37%. Total cardiovascular-related hospital days were reduced by 26% (p = 0.025). The between-group offset in direct medical costs was $524, which resulted in a 11% cost offset of lovastatin therapy over the mean study duration of 5.2 years. Lovastatin provides meaningful reductions in cardiovascular-related resource utilization and reductions in direct cardiovascular-related costs associated with the onset of coronary disease.

Serial acquisition of data to predict one-year mortality rate after acute myocardial infarction.

Eight hundred sixty-six patients with acute myocardial infarction (AMI) were enrolled in a prospective study to determine optimal predictors of long-term prognosis. During 12-month (mean) follow-up there were 65 cardiac deaths and 21 nonfatal repeat AMIs. Twenty-nine variables (from the history, physical examination, serum chemistries, ambulatory monitor, radionuclide ventriculogram and exercise test) were arranged into in 5 sequential groups according to the time at which results became available during hospitalization. Multivariate analysis (logistic regression) and receiver-operator characteristic curves were used to assess improvement in prediction of mortality or repeat AMI by addition of each group of variables. The first group of independent predictors included rales, left bundle branch block and symptom status at 1 month before admission. Addition of information from ambulatory monitoring or serum chemistry did not improve prediction. Radionuclide ejection fraction made a statistically significant, independent contribution to mortality prediction. Of the final group the only exercise test variable that contributed independently to prediction was whether the patients took the test. However, receiver-operator characteristic curves showed that improvement in sensitivity and specificity by addition of information from the radionuclide scan and exercise test was clinically insignificant. Our results imply that costly tests after AMI should be reserved for specific indications and not applied universally for prognosis. Although these tests were highly predictive individually, each test generally added little to preexisting prognostic information.

Background and methods for the lovastatin restenosis trial after percutaneous transluminal coronary angioplasty. The Lovastatin Restenosis Trial Study Group.

Restenosis remains a critical limitation of percutaneous transluminal coronary angioplasty (PTCA). Recent experimental and clinical data have suggested that lovastatin, an hydroxymethylglutaryl coenzyme A reductase inhibitor, may reduce the rate of restenosis through reduction of low density-lipoprotein (LDL) cholesterol or possibly by direct effects. Lovastatin may therefore produce favorable alterations in endothelial healing, resulting in a decreased smooth muscle cell proliferative response to injury after angioplasty. Emory University, in conjunction with Merck Research Laboratories, has initiated a 10-center double-blinded, placebo-controlled, randomized trial to assess the effect of both pretreatment and aggressive lipid lowering with lovastatin in reducing the rate of restenosis. Lovastatin achieves approximately 75% of its effect on LDL cholesterol by 1 week. Thus, patients scheduled for PTCA are randomly assigned pretreatment with lovastatin, 40 mg twice daily, or placebo 7 to 10 days before PTCA. Therapy is continued for 6 months, at which time repeat coronary arteriography is performed. A detailed safety algorithm was designed, with patients receiving lovastatin and matching placebo back-titrated on a 1:1 basis for LDL cholesterol less than 50 mg/dl. The power is a 90%, alpha = 0.05, 2-tailed test to reduce restenosis from 30 to 15%. The sample size is 360 patients in the 2 arms; allowing for a 10% dropout rate, approximately 400 patients will be randomized. Patients with successful PTCA, less than 50% residual diameter stenosis and greater than or equal to 20% diameter stenosis reduction are analyzed for restenosis at 4 to 6 months by quantitative coronary arteriography.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation of lumen size to restenosis after percutaneous transluminal coronary balloon angioplasty. Lovastatin Restenosis Trial Group.

The relation between post-percutaneous transluminal balloon angioplasty (post-PTCA) and angiography indexes were investigated in the Lovastatin Restenosis Trial. Post-PTCA percent diameter measured by the operator was found to be a weak predictor of angiographic and clinical follow-up restenosis.

Analysis of the degree of undertreatment of hyperlipidemia and congestive heart failure secondary to coronary artery disease.

There is a lack of data evaluating the implementation of guidelines in the management of coronary artery disease (CAD) or congestive heart failure (CHF) in the outpatient setting. We analyzed an administrative data set from the Merck & Co. sponsored national Quality Assurance Program, a retrospective outpatient chart audit of 58,890 adult outpatients from 140 medical practices (80% cardiology only) in the USA with diagnoses of CAD and/or CHF identified from medical claims data. We determined the (1) frequency of lipid documentation and prescription of lipid-lowering agents in patients with CAD, (2) frequency of assessment of left ventricular function and prescription of an angiotensin-converting enzyme inhibitor in patients with CHF, and (3) predictors of medication prescription. Of the 48,586 patients with CAD, 44% had annual diagnostic testing of low-density lipoprotein cholesterol. Only 25% of these patients reached the target low-density lipoprotein cholesterol of < or = 100 mg/dl, and only 39% were taking lipid-lowering therapy, which was less among the elderly than in the younger patients. Of the 16,603 patients with CHF, 64% had diagnostic testing of left ventricular function, and 50% of patients were taking an angiotensin-converting enzyme inhibitor; 67% of patients received medication if they had documented systolic dysfunction. Significant predictors of medication prescription included diagnostic testing, younger age, history of myocardial infarction or coronary artery bypass grafting, hypertension, cardiology specialty, and geographic region. Thus, current practice patterns in the management of CAD and CHF are inadequate. Patient age, diagnostic testing, and practice environment influence medication prescription.

Performance assessment model for guideline-recommended pharmacotherapy in the secondary prevention of coronary artery disease and treatment of left ventricular dysfunction.

The Agency for Health Care Policy and Research, the National Heart Lung and Blood Institute of the National Institutes of Health, the American Heart Association, and the American College of Cardiology have all developed guidelines for improving the care of patients with cardiovascular disease. The guidelines include recommendations for intensive lipid-lowering therapy in patients with coronary artery disease (CAD) and angiotensin-converting enzyme (ACE) inhibitors in those patients with symptomatic heart failure and asymptomatic left ventricular dysfunction. Despite clinical trial evidence and consensus that these therapies improve survival in high-risk patients, data suggest that there is wide variation in the delivery of guideline-based care. To investigate whether evidence-based assessment of provider practice patterns can impact the delivery of quality cost-effective care, Merck and Company, in conjunction with leading cardiology group practices, the University of North Carolina at Chapel Hill, and Medical Review of North Carolina developed an ambulatory medical record abstraction study. This quality assurance initiative was conducted at practices beginning in the spring of 1996 and continues. Medical records and administrative claims of patients with ischemic heart disease or heart failure were abstracted by a healthcare consulting organization to maintain patient and physician confidentiality. As of mid-July 1997, 626 group practices had completed the medical record abstraction process, with > 1,136 practices participating at some stage of the project; >6,000 physicians participated in the project and >270,000 patients charts were abstracted. Analysis of these data will provide insight and benchmark patterns of care in the pharmacologic management of heart failure and CAD. This project represents a unique collaboration between a pharmaceutical company, an academic institution, a Peer Review Organization, and practicing physicians, to support evidence-based best medical practices.

Performance standards and edge detection with computerized quantitative coronary arteriography. The Lovastatin Restenosis Trial Group.

Quantitative coronary angiography (QCA) has become an important tool for evaluating coronary angiograms. Many methodologic factors, such as the choice of frame to analyze, the selection of the "normal," segment and the method of edge detection used may affect the results of QCA. The sequential steps in performing QCA, including a comparison of visual and automated edge-detection methodologies, were evaluated using 12 precision-drilled phantoms and 20 patient films. Normal diameter, minimal lumen diameter, and diameter stenosis were measured. In the phantom studies, the measurements from both visual and automated systems correlated well with the true measurements of the phantoms and between systems (all r values >0.92). To study the difference between methodologies on QCA results as influenced by the choice of frame and normal segment analyzed, the patient films were analyzed independently in 3 separate rounds of interpretation. In round 1, each system's operator individually chose frames and normal segments for analysis. In round 2, both systems analyzed the same preselected frames, but independently chose normal segments. In round 3, both systems analyzed the same preselected normal segments and frames. The intersystem correlations between visual and automatic systems for rounds 1, 2, and 3 were: normal diameter, r = 0.25, r = 0.37, and r = 0.75, respectively; minimal lumen diameter, r = 0.79, r = 0.86, and r = 0.85, respectively; and diameter stenosis, r = 0.65, r = 0.73, and r = 0.87, respectively. The manual edge-detection and automated edge-detection systems used in this study are reasonably accurate and consistent on phantom studies. In patient studies, the nonautomated processes (choice of frame and normal segment for analysis) produced significant differences in the QCA results, thus illustrating that operator-dependent factors other than edge detection are very important in QCA.

Can cardiovascular clinical characteristics be identified and outcome models be developed from an in-patient claims database?

The objective of this study was to assess whether administrative (claims) databases can be used to assess clinical variables and predict outcome. Although administrative databases are useful for assessing resource utilization, their utility for assessing clinical information is less certain. Prospectively gathered clinical databases, however, are expensive and not widely available. The UB92 formulation of the hospital bill was used as an administrative source of data and compared with the clinical cardiovascular database at Emory University. The claims database was compared with the clinical database for 11 variables. Outcome models were developed with multivariate methods. A total of 11,883 patients who underwent catheterization (5,255 underwent percutaneous transluminal coronary angioplasty [PTCA] and 3,794 underwent coronary artery bypass surgery [CABG]) between 1991 and 1995 were included. For some variables, the claims database correlated well (diabetes, sensitivity 87%, specificity 99%), whereas for others the claims database was less accurate (peripheral vascular disease, sensitivity 20%, specificity 99%). Uncertain coding in the claims database, which can result in the same code being used for co-morbid states and severity of disease, as well as complications, limited the ability of claims to predict outcome. Clinical databases may also be limited by lack of objectivity and missing data. The utility of claims databases to assess severity of disease and co-morbid states is limited, and outcome modeling and risk assessment from claims databases may be inappropriate and spurious. Developing better data standards and less expensive methods for acquisition of clinical data is necessary for improved outcome assessment.

Economics, health-related quality of life, and cost-effectiveness methods for the TACTICS (Treat Angina With Aggrastat [tirofiban]] and Determine Cost of Therapy with Invasive or Conservative Strategy)-TIMI 18 trial.

Concern over escalating health care costs has led to increasing focus on economics and assessment of outcome measures for expensive forms of therapy. This is being investigated in the Treat Angina With Aggrastat [tirofiban] and Determine Cost of Therapy with Invasive or Conservative Strategy (TACTICS)-TIMI 18 trial, a randomized trial comparing outcome of patients with unstable angina or non-Q-wave myocardial infarction treated with tirofiban and then randomized to an invasive versus a conservative strategy. Hospital and professional costs initially and over 6 months, including outpatient costs, will be assessed. Hospital costs will be determined for patients in the United States from the UB92 formulation of the hospital bill, with costs derived from charges using departmental cost to charge ratios. Professional costs will be determined by accounting for professional services and then converted to resource units using the Resource Based Relative Value Scale and then to costs using the Medicare conversion factor. Follow-up resource consumption, including medications, testing and office visits, will be carefully measured with a Patient Economic Form, and converted to costs from the Medicare fee schedule. Health-related quality of life will be assessed with a specific instrument, the Seattle Angina Questionnaire, and a general instrument, the Health Utilities Index at baseline, 1, and 6 months. The Health Utilities Index will also be used to construct a utility. By knowing utility and survival, quality-adjusted life years will be determined. These measures will permit the performance of a cost-effectiveness analysis, with the cost-effectiveness of the invasive strategy defined and the difference in cost between the invasive and conservative strategies divided by the difference in quality-adjusted life years. The economic and health-related quality of life aspects of TACTICS-TIMI 18 are an integral part of the study design and will provide a comprehensive understanding of the impact of invasive versus conservative management strategies on a broad range of outcomes after hospitalization for unstable angina or non-Q-wave myocardial infarction.

Use of hydrofluoroalkane propellant delivery system for inhaled albuterol in patients receiving asthma medications.

OBJECTIVE: This study was undertaken to assess drug-use patterns associated with albuterol delivery via a new propellant device compared with conventional chlorofluorocarbon (CFC) metered-dose inhalers (MDIs) in patients taking asthma medications in a population with pharmacy benefits. BACKGROUND: In addition to their ozone-depleting properties, conventional CFC inhalers often deliver inconsistent doses because of loss of prime and temperature instability. A new propellant, hydrofluoroalkane (HFA), incorporates a re-engineered delivery system associated with dosing reproducibility throughout the life of the canister. METHODS: Drug markers associated with management of asthma were used to identify a study cohort of new users of inhaled albuterol from a geographically diverse pharmacyclaims database from July 1, 1997, through December 31, 1997. A population of 282,879 members was identified over the 20-month follow-up period. In addition, a subset of chronic albuterol inhaler users (> or = 12 months; n = 96,879) was also identified to support a longitudinal analysis. Disease severity was controlled for by use of inhaled corticosteroids (ICS). To control for canisters received via physician office samples, HFA patient use was corrected by a physician-based canister adjustment based on HFA sample data. RESULTS: A total of 53.1% of participants were women and 46.1% were men; most of the population (72.5%) was <65 years of age. Canister use for HFA patients was consistently lower (2.7+/-3.2 vs 5.4+/-6.7) than for CFC MDIs for the entire cohort over the 20-month assessment period. This difference was consistently observed for albuterol canister use in patients with and without concomitant ICS use (3.3+/-3.8 HFA vs 7.2+/-7.5 CFC for ICS users and 2.1+/-2.1 HFA vs 4.1+/-5.7 CFC for non-ICS users). Time to next prescription also was longer for HFA patients than for CFC patients (61.6+/-50.9 days HFA vs 47.3+/-40.8 days CFC). When duration of therapy and physician samples associated with product launch were controlled for, similar differences were consistently observed. CFC patients used, on average, 1.3 more canisters per year than did HFA patients (P < 0.001), averaging 10.7 canisters (95% CI, 10.6 to 10.7), compared with 9.4 canisters used by HFA patients (95% CI, 8.9 to 9.9). Further analyses indicated that this finding was consistent when ICS use was controlled for (CFC plus ICS mean, 11.9 canisters vs HFA plus ICS mean, 10.4 canisters; P < 0.001). CONCLUSION: This study provides useful information about the effect of use of a new albuterol delivery system on asthma inhaler management. These data suggest that CFC patients use an average of 1.3 more canisters per year compared with HFA patients independent of asthma severity as measured by ICS use. This improvement in dosing characteristics has the potential to translate into enhanced economic outcomes.